Studies of the occurrence of mental illness in families have been useful in identifying familial forms of the illnesses and in the development of hypotheses regarding the nature and strength of genetic and environmental factors in etiology. Where these factors are separated by the process of adoption, specific etiologic hypotheses can be tested separately and in combination. As reported in previous annual reports, classical schizophrenia and schizophrenia-like disorders occur at a significantly elevated rate in the biological relatives of chronic schizophrenic adoptees and not in their adoptive relatives, a finding now replicated in our national register of the nearly 15,000 Danish adoptees who have reached maturity. This provides compelling evidence for the significant operation of genetic factors in the etiology of this disorder. Our demonstration that the increased prevalence of schizophrenia in the biological families of adoptees does not differ significantly from that found in the natural families of schizophrenics indicates that the well established familial tendency in this disorder is an expression of genetic factors, and provides hitherto lacking justification for the use of family studies to examine the modes of genetic transmission and to search for genetic linkage in large pedigrees of naturally reared schizophrenics.